Hormesis & biphasic response

[Guest guest]

Hi All & Hi Sammy,

 

Sammy, great stuff on hormesis/biphasic response.

 

There are many examples of biphasic or paradoxical responses in

AP, for example ST36 in gastric spasm and gastric atony.

 

Could it be that the sensitised system " takes what it needs " from

the same stimulus in two oppisite situations?

 

Best regards,

Phil

 

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

 

Sammy wrote:

 

Science is a template for acquiring certainty in knowledge. From

the Empiricist tradition; Popper; and Kuhn and the expression of

this in the mathematical statistics notion of P values to determine

the 'Absence of Verification of the Null Hypothesis' (rather than a

'Proof of the Hypothesis' itself which is impossible) .. we acquire a

methodology that gives us this certainty that no other methodology

in the history of civilisation has done. Let's not forget that when we

knock western Science.

 

On the other hand this Science is as Emmanual observed a

template for the pedantic and unimaginative, which I see has

spawned a ponderous monolith we know as 'the research industry'.

Despite the shortcomings there is still room for originality, creativity

and intuition in Science. I think a good example is found in

development of the notion of hormesis in toxicology. Somehow

these ideas are squeezing into the rigid template, opining it up and

making it possible to 'do science' in a TCM context, AND to have

an eye for the criteria Jim points out. Sammy.

 

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

 

Hormesis is a non-linear biological response to a substance. " low-

dose stimulation and a high-dose inhibition " [1].

 

Calabrese, admits the phenomenon has been marginalised in the

west because of the inability to fit it into the current scientific

paradigm, regardless of its empirical reality[2].

 

From my own area of interest: I regarded the biphasic response of

prostate cells to androgens as a specialised adaptation; now it

appears that hormesis is a general phenomenon which may

eventually acquire conventional clinical acceptance[3].

 

The rationale for treating prostate cancer in TCM as a disease of

deficiency rather than one of excess grows, despite the increasing

practice of 'castration therapy' in China for the problem, and the

continued popularity of 'TCM-like' PC-SPES analogs in the west.

That each views the others medicine in a framework of parody is

hopefully a temporary disorder: incoherence1 (not incoherence2).

 

Refs: http://www.ncbi.nlm.nih.gov/entrez/

 

1: Toxicol Sci. 2003 Feb;71(2):246-50. Related Articles, Links

Comment on: Toxicol Sci. 2003 Feb;71(2):134-6. The hormetic

dose-response model is more common than the threshold model in

toxicology. Calabrese EJ, Baldwin LA. Department of

Environmental Health Sciences, University of Massachusetts,

Amherst, Massachusetts 01003, USA.

edwardc The threshold dose-response

model is widely viewed as the most dominant model in toxicology.

The present study was designed to test the validity of the threshold

model by assessing the responses of doses below the

toxicological NOAEL (no observed adverse effect level) in

relationship to the control response (i.e., unexposed group). Nearly

1,800 doses below the NOAEL, from 664 dose-response

relationships derived from a previously published database that

satisfied a priori entry criteria, were evaluated. While the threshold

model predicts a 1:1 ratio of responses " greater than " to " less

than " the control response (i.e., a random distribution), a 2.5:1 ratio

(i.e., 1171:464) was observed, reflecting 31% more responses

above the control value than expected (p < 0.0001). The mean

response (calculated as % control response) of doses below the

NOAEL was 115.0% +/- 1.5 standard error of the mean (SEM).

These findings challenge the long-standing belief in the primacy of

the threshold model in toxicology (and other areas of biology

involving dose-response relationships) and provide strong support

for the hormetic-like biphasic dose-response model characterized

by a low-dose stimulation and a high-dose inhibition. These

findings may affect numerous aspects of toxicological and

biological/biomedical research related to dose-response

relationships, including study design, risk assessment, as well as

chemotherapeutic strategies. PMID: 12563110 [PubMed - indexed

for MEDLINE]

 

2. Hum Exp Toxicol. 2000 Jan;19(1):32-40. The marginalization of

hormesis. Calabrese EJ, Baldwin LA. Department of Environmental

Health Sciences, School of Public Health, University of

Massachusetts, Amherst, MA 01003, USA. Despite the

substantial development and publication of highly reproducible

toxicological data, the concept of hormetic dose-response

relationships was never integrated into the mainstream of

toxicological thought. Review of the historical foundations of the

interpretation of the bioassay and assessment of competitive

theories of dose-response relationships lead to the conclusion that

multiple factors contributed to the marginalization of hormesis

during the middle and subsequent decades of the 20th century.

These factors include: (a) the close-association of hormesis with

homeopathy lead to the hostility of modern medicine toward

homeopathy thereby creating a guilt by association framework, and

the carry-over influence of that hostility in the judgements of

medically-based pharmacologists/ toxicologists toward hormesis;

(b) the emphasis of high dose effects linked with a lack of

appreciation of the significance of the implications of low dose

stimulatory effects; © the lack of an evolutionary-based

mechanism(s) to account for hormetic effects; and (d) the lack of

appropriate scientific advocates to counter aggressive and

intellectually powerful critics of the hormetic perspective.

Publication Types: Review Review, Tutorial PMID: 10745293

[PubMed - indexed for MEDLINE]

 

3. Crit Rev Toxicol. 2003;33(3-4):305-53. Related Articles, Links

Chemotherapeutics and hormesis. Calabrese EJ, Baldwin LA.

Department of Environmental Health Sciences, Morrill Science

Center, University of Massachusetts, Amherst, MA 01003, USA.

edwardc This article represents the first

comprehensive assessment of hormetic effects of

chemotherapeutic agents. Hormetic dose-response relationships

were reported for a wide range of chemotherapeutics, including

antibiotics, antiviral, and antitumor agents as well as substances

that affect hair growth, prostate function, cognitive performance,

and numerous other endpoints. Particular attention was given to

assessing the quantitative features of the dose response, the

underlying mechanistic features of the biphasic nature of the dose

response, and the clinical implications of hormetic responses.

Recognition of the hormetic-like biphasic nature of the dose

response is expected to have an important impact on the design of

experiments to assess chemotherapeutics and how such agents

may be employed more successfully in clinical applications.

Publication Types: Review Review, Tutorial PMID: 12809428

[PubMed - indexed for MEDLINE]

 

Best regards,

 

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